Hypoxanthine-Leu-Met-COOH (RM06) affects haemotopoietic reconstitution and natural killer cell activity in mice transplanted with syngeneic bone marrow

The in vivo effects of a new hypoxanthine-peptidyl derivative (RM06) on haemopoietic reconstitution and natural killer (NK) cell activity were evaluated in mice undergoing syngeneic bone marrow transplantation (SBMT). Lethally irradiated BDF-1 mice were injected i.v. with 10⁷ syngeneic bone marrow cells. Animals were treated from day + 1 to + 3 after SBMT with RM06 (1 mg/kg). Controls were treated i.p. with murine recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF, 100 U/mouse) or with saline as placebo. Colony forming units (CFU-GMs) were evaluated at days + 7, + 10, + 14, + 17 and + 21 after SBMT both from the spleen and bone marrow. The NK cell activity of the spleen was also evaluated. RM06 was found to be capable of enhancing significantly both the number of splenocytes and of bone marrow cells. Moreover, CFU-GMs were also significantly augmented by RM06 treatment both in the spleen and bone marrow, the maximal effect being observed at day + 10. In addition, the NK activity, as evaluated in vitro against YAC-1 murine lymphoma cells, was also significantly augmented. It is concluded that the new peptidyl-hypoxanthine derivative RM06 is capable of reproducing in vivo some of the effects achievable with GM-CSF. RM06 induces the expansion of bone marrow progenitor cells, resulting in a shorter time of aplasia and recovery of the NK function.